Aspects of genetics in paediatrics : scientific proceedings of the 3d Unigate Workshop held at the Royal College of Physicians, St. Andrew's Place, London, May 1975 / edited by Donald Barltrop.

  • Unigate Paediatric Workshop 1975 : London, England)
Date:
1976
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Licence: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)

Credit: Aspects of genetics in paediatrics : scientific proceedings of the 3d Unigate Workshop held at the Royal College of Physicians, St. Andrew's Place, London, May 1975 / edited by Donald Barltrop. Source: Wellcome Collection.

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    The genetics of alpha-l-antitrypsin and its implications MAGNE К. FAGERHOL Blood Bank and Department of Immunohaematology, Ullevaal Hospital, Oslo 1, Norway It is appropriate to select alpha-l-antitrypsin (AA) polymorphism for discussion during this workshop. This is an expanding field that has implications for clinical paediatrics, for basic theories on protein synthesis and secretion, the biochemistry of inflam¬ mation, and for fundamental genetics. Molecular genetics Alpha-l-antitrypsin is responsible for the distinct alpha-l-globulin zone on serum electrophoresis in agarose gels, pH 8-6 (Fig. 1). It is found in a con¬ centration of 210-250 mg/100 ml in normal serum, which amounts to about 3-5% of the total protein. Lack of the protein predisposes to fatal diseases which testifies to the biological importance of the protein. Despite its name, trypsin is not an important target for inhibition by AA in vivo. Elastase and collagenase from leucocytes and macrophages are more likely candidates. The protein has received its name because it is responsible for about 90% of the total serum trypsin inhibitory capacity. In addition, it can inhibit many proteases involved in the clotting and fibrinolytic systems (factor XI—plasma throm¬ boplastin antecedent, thrombin, plasmin), digestive enzymes (chymotrypsin), and some bacterial en¬ zymes. The first report of genetic variation in AA dates back to 1964 when Eriksson reported that the AA deficiency associated with pulmonary emphysema was inherited. During the next 10 years, mainly by use of a highly sensitive starch gel electrophoretic method (Fagerhol and Braend, 1965, Fagerhol, 1968), it was demonstrated that the deficiency gene was only one out of more than twenty inherited variants of AA. These are included in a serum type system, the Pi system (Fig. 2). The symbol Pi for the system was chosen since AA is a potent protease MM MZ FM MV tti-antitrypsin Fig. 1. Serum electrophoresis in agarose gel, pH 8-6. The distinct zone in the alpha-l-globulin region is due to alpha-l-antitrypsin. To the right the FM and MV genetic variants give two zones, while serum from individuals heterozygous for the deficiency gene, MZ, give a single zone with about half the normal staining intensity. inhibitor. Only the two major out of a total of eight AA zones which can be detected on electrophoresis of serum in starch gels, pH 4-95, are shown. On agarose gel electrophoresis at pH 8-6 however, the allele product is one major and one minor zone. The 73